BioModelsapplication/xmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000053?filename=curation_notes.txthttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000053?filename=BIOMD0000000053.pdfhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000053?filename=BIOMD0000000053-biopax3.owlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000053?filename=BIOMD0000000053-biopax2.owlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000053?filename=BIOMD0000000053_url.xmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000053?filename=manifest.xmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000053?filename=BIOMD0000000053-matlab.mhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000053?filename=BIOMD0000000053_url.sedmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000053?filename=BIOMD0000000053.vcmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000053?filename=curation_image.pnghttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000053?filename=BIOMD0000000053-octave.mhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000053?filename=BIOMD0000000053.mhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000053?filename=BIOMD0000000053.scihttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000053?filename=BIOMD0000000053.odehttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000053?filename=metadata.rdfhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000053?filename=BIOMD0000000053.pngprimaryOK200Harish DharuriManually curatedordinary differential equation modelAmyloidosisDiabetes MellitusL2V3https://www.ebi.ac.uk/biomodels/BIOMD000000005312911334falseBioModelsSBMLModelsFerreira2003 CML generation22003MODEL0733584307António E N Ferreira, Ana M J Ponces Freire, Eberhard O VoitAntónio E N Ferreira12911334, The Maillard reaction between reducing sugars and amino groups of biomolecules generates complex structures known as AGEs (advanced glycation endproducts). These have been linked to protein modifications found during aging, diabetes and various amyloidoses. To investigate the contribution of alternative routes to the formation of AGEs, we developed a mathematical model that describes the generation of CML [ N(epsilon)-(carboxymethyl)lysine] in the Maillard reaction between glucose and collagen. Parameter values were obtained by fitting published data from kinetic experiments of Amadori compound decomposition and glycoxidation of collagen by glucose. These raw parameter values were subsequently fine-tuned with adjustment factors that were deduced from dynamic experiments taking into account the glucose and phosphate buffer concentrations. The fine-tuned model was used to assess the relative contributions of the reaction between glyoxal and lysine, the Namiki pathway, and Amadori compound degradation to the generation of CML. The model suggests that the glyoxal route dominates, except at low phosphate and high glucose concentrations. The contribution of Amadori oxidation is generally the least significant at low glucose concentrations. Simulations of the inhibition of CML generation by aminoguanidine show that this compound effectively blocks the glyoxal route at low glucose concentrations (5 mM). Model results are compared with literature estimates of the contributions to CML generation by the three pathways. The significance of the dominance of the glyoxal route is discussed in the context of possible natural defensive mechanisms and pharmacological interventions with the goal of inhibiting the Maillard reaction in vivo.. Pt 1, 376. Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade de Lisboa, Bloco C8, Campo Grande, 1749-016 Lisboa, Portugal. aeferreira@fc.ul.pthdharuri@cds.caltech.eduCalifornia Institute of TechnologyBIOMD0000000053The Maillard reaction between reducing sugars and amino groups of biomolecules generates complex structures known as AGEs (advanced glycation endproducts). These have been linked to protein modifications found during aging, diabetes and various amyloidoses. To investigate the contribution of alternative routes to the formation of AGEs, we developed a mathematical model that describes the generation of CML [ N(epsilon)-(carboxymethyl)lysine] in the Maillard reaction between glucose and collagen. Parameter values were obtained by fitting published data from kinetic experiments of Amadori compound decomposition and glycoxidation of collagen by glucose. These raw parameter values were subsequently fine-tuned with adjustment factors that were deduced from dynamic experiments taking into account the glucose and phosphate buffer concentrations. The fine-tuned model was used to assess the relative contributions of the reaction between glyoxal and lysine, the Namiki pathway, and Amadori compound degradation to the generation of CML. The model suggests that the glyoxal route dominates, except at low phosphate and high glucose concentrations. The contribution of Amadori oxidation is generally the least significant at low glucose concentrations. Simulations of the inhibition of CML generation by aminoguanidine show that this compound effectively blocks the glyoxal route at low glucose concentrations (5 mM). Model results are compared with literature estimates of the contributions to CML generation by the three pathways. The significance of the dominance of the glyoxal route is discussed in the context of possible natural defensive mechanisms and pharmacological interventions with the goal of inhibiting the Maillard reaction in vivo.A quantitative model of the generation of N(epsilon)-(carboxymethyl)lysine in the Maillard reaction between collagen and glucose.Ferreira António E N AE, Ponces Freire Ana M J AM, Voit Eberhard O EOModb1, Myelocytic, biochemical pathways, Chronic Myelocytic Leukemia, Bru, Chronic Granulocytic Leukemia, Collagens, Raw, Chronic Myeloid Leukemia, Lysine Hydrochloride, Myeloid, Glukose, Myelocytic Leukemia, Monohydrate, Aging, Philadelphia-Positive Myeloid Leukemias, (DL)-Isomer, Pi, systemic amyloidosis, chronic myelogenous, Lysine Acetate, Non-Enzymatic, Biological, Dextrose, 2, cellular degradation, Ph1 Positive, hydrazinecarboximidamide, Zyderm, Leprb, DM - Diabetes mellitus, multicellular organismal biosynthetic process, L Lysine, BCR1, Chronic Myelocytic Leukemias, Svc, Senescence, amyloidosis, single-organism biosynthetic process, tetraoxophosphate(V), me75, Orthophosphate, K, PHOSPHATE ION, catabolism, tetraoxidophosphate(3-), Microfibril Collagen Hemostat, Chronic Myelogenous Leukemias, epsilon-diaminocaproic acid, Myelogenous Leukemia, Phosphate, adult chronic leukaemia, D17Mit170, DL-glucose, T1, Food, Granulocytic, glucose, Biological Aging, reaction, Diabetes mellitus, LYS, collagen, Reaction, Lysin, Collagen Fleece, adult chronic leukemia, Ph1-Positive Myeloid Leukemia, biotransformation, Collagen, Inorganic, db, Amyloidoses, Myelogenous, Granulocytic Leukemias, DM, aminoguanidine, Ph1-Positive Myelogenous Leukemia, Philadelphia-Positive, Tl3, Tl2, results, OB-RGRP, Literatures, Ph1-Positive, D22S662, Lipid Glycation, Browning Reactions, Ph1-Positive Myeloid Leukemias, Philadelphia-Positive Myeloid, aminoguanidine sulfate, Lipid, lysine, NOS, secretion, (alpha-D)-Isomer, Phosphates, D-Glucose, Chronic granulocytic leukemia, Non-Enzymatic Glycosylation, amyloidoses, Chronic Granulocytic, Chronic Myelogenous, Chronic Myeloid Leukemias, PO4(3-), Glycation, Ph1-Positive Myelogenous, Ph1-Positive Myeloid, alpha, Obr, Diabetes NOS, chronic granulocytic leukemia, phosphate, D Glucose, phosphate ions, CML - chronic Myelogenous Leukemia, Collagen Felt, monoaminoguanidine, obl, Glucose Monohydrate, Fructation, Myelogenous Leukemias, gluco-hexose, CLL, tetraoxophosphate(3-), Philadelphia Positive, Glucose, Goal, alpha-Collagen, chronic granulocytic leukaemia, cellular catabolism, Buffer, CML, Non-Enzymatic Glycation, Microfibril, Glycosylation, Dermodress, Glucation, Collastat, Diabetes mellitus (disorder), amyloid, atypical, Philadelphia-Positive Myeloid Leukemia, Lysine, Del(8)44H, Low, Nonenzymatic, Chronic Granulocytic Leukemias, chronic myeloid, Leukemia, breakdown of chemical, D22S11, amyloidosis (disease), Granulocytic Leukemia, Inorganic Phosphates, Avitene, obese-like, PHL, Ethanedial, alpha Collagen, Ethanedione, Ph1-Positive Myelogenous Leukemias, Food Browning, Myeloid Leukemia, Myelocytic Leukemias, Chronic, Browning Reaction, Collagenfleece, Diabetes, Anhydrous, diabetes, ALL, leukemia, [PO4](3-), Non Enzymatic Glycation, cellular breakdown, cou, (beta-D)-Isomer, degradation, Chronic Myelocytic, pimagedine hydrochloride, buffer, Protein Glycation., Leukemias, chronic, Non Enzymatic Glycosylation, diabetes mellitus (disease), Lr, Chronic myelogenous leukemia, chronic myelogenous leukemia, Acetate, Nonenzymatic Protein Glycation, Protein, Myeloid Leukemias, Collagen Hemostat, Browning, L-Lysine, Ribation, amyloid disease, Pangen, breakdown of molecule, Inorganic Phosphate, LEPROT, Xcml, Col4a-1, Reactions, Chronic Myelogenous Leukemia, biodegradation, diabetes mellitus, other collagen, cml-A, Avicon, Sugar, Anhydrous Dextrose, breakdown of substance, chronic myelogenous leukaemia, chronic myeloid leukaemia, Bra, Maillard, phosphates, 6-diaminohexanoic acid, Enisyl, Chronic Myeloid, Protein Glycation, GlcMyelogenous Leukemias, Myelocytic, extent, CLL, Chronic Myelocytic Leukemia, Sectors, Chronic Granulocytic Leukemia, Public Sectors, Philadelphia Positive, YB, Lysine Hydrochloride, Chronic Myeloid Leukemia, Myeloid, AUTSX5, number, Myelocytic Leukemia, Copyrights, chronic granulocytic leukaemia, NOVH, Philadelphia-Positive Myeloid Leukemias, CCN3, QM, CML, Lysine Acetate, chronic myelogenous, Yb, 2, Lysine, Ph1 Positive, atypical, Philadelphia-Positive Myeloid Leukemia, Public Enterprise, Enterprises, CG2706, fs(1)M104, L Lysine, multicellular organismal biosynthetic process, BCR1, Chronic Myelocytic Leukemias, Chronic Granulocytic Leukemias, single-organism biosynthetic process, chronic myeloid, Leukemia, K, D22S11, Granulocytic Leukemia, Public Domains, epsilon-diaminocaproic acid, Chronic Myelogenous Leukemias, Myelogenous Leukemia, PHL, IGFBP9, Public Enterprises, adult chronic leukaemia, Granulocytic, IBP-9, Kiaa4053, LYS, Ph1-Positive Myelogenous Leukemias, L10, Lysin, Myeloid Leukemia, Myelocytic Leukemias, adult chronic leukemia, Ph1-Positive Myeloid Leukemia, Chronic, NOVh, Enterprise, ALL, Myelogenous, leukemia, Granulocytic Leukemias, completeness, Chronic Myelocytic, DmelCG2706, Ph1-Positive Myelogenous Leukemia, DXS648, Philadelphia-Positive, Leukemias, chronic, presence., Ph1-Positive, D22S662, Ph1-Positive Myeloid Leukemias, count in organism, Chronic myelogenous leukemia, chronic myelogenous leukemia, IGFBP-9, Acetate, Public, Public Domain, Philadelphia-Positive Myeloid, Myeloid Leukemias, lysine, Domains, NOV, L-Lysine, PlexA1, Domain, Data Base, Xcml, Chronic granulocytic leukemia, Plxn1, Chronic Granulocytic, Chronic Myelogenous, Chronic Myelogenous Leukemia, Chronic Myeloid Leukemias, cml-A, Ph1-Positive Myelogenous, nov, Ph1-Positive Myeloid, alpha, mKIAA4053, fs(1)Y[b], chronic granulocytic leukemia, Sector, chronic myelogenous leukaemia, C130088N23Rik, CML - chronic Myelogenous Leukemia, chronic myeloid leukaemia, EG:95B7.8, 2600013D04Rik, PLXN1, DXS648E, 6-diaminohexanoic acid, Enisyl, Chronic Myeloidgluco-hexose, Non Enzymatic Glycation, Collagens, (beta-D)-Isomer, Lysine Hydrochloride, Glucose, Glukose, number, alpha-Collagen, Monohydrate, (DL)-Isomer, presence, Non Enzymatic Glycosylation, Lipid Glycation, count in organism, Browning Reactions, Lysine Acetate, Non-Enzymatic, Non-Enzymatic Glycation, Microfibril, Glycosylation, Acetate, Dermodress, Glucation, Collastat, Lipid, Nonenzymatic Protein Glycation, Protein, Dextrose, lysine, Collagen Hemostat, 2, Browning, Lysine, Zyderm, (alpha-D)-Isomer, L-Lysine, Ribation, Pangen, L Lysine, Nonenzymatic, D-Glucose, Non-Enzymatic Glycosylation, Reactions, K, Glycation, other collagen, Microfibril Collagen Hemostat, Glc., Avitene, epsilon-diaminocaproic acid, Avicon, alpha, alpha Collagen, DL-glucose, Anhydrous Dextrose, Food, glucose, LYS, collagen, D Glucose, Lysin, Reaction, Collagen Fleece, Food Browning, Collagen Felt, Browning Reaction, Maillard, Collagen, 6-diaminohexanoic acid, Glucose Monohydrate, Collagenfleece, Enisyl, Fructation, Anhydrous, Protein GlycationfalseFerreira2003_CML_generation2 The model should reproduce the figure 2F of the article. The equation 7 has been split into equations 7a-7c, in order to take into account the different flux rates of Lysine and CML formation from Schiff. The model was tested in Jarnac (SBML L2 V1) and Copasi (SBML L2 V3). To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information. In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not. To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92. 2024-08-212024-09-022006-04-09BIOMD000000005312911334CHEBI:17234CHEBI:25094CHEBI:34779MODEL0733584307BIOMD0000000053GO:0005518GO:0018205C00293C14448131567